Studies of hormonal responses to neuroendocrine challenge procedures have produced highly promising results in patients with major depressive disorder. There is a long history of interest in serotonergic mechanisms in depression. Moreover, a substantial body of data from both animal and clinical studies implicates serotonin in the control of several neuroendocrine axes. L-tryptophan, the amino acid precursor of serotonin, may provide an effective means to stimulate hormonal secretion via activation of serotonergic pathways. This method could be applied productively in studies of depressed patients. To date, clinical studies of the effects of l-tryptophan (TP) administration on hormonal responses have provided inconsistent results. We believe that these inconsistencies may be explained by differences in methodology among different studies, pertaining to such experimental conditions as dose, route of administration, sex, etc. Here, we propose to conduct systematic studies of intravenous infusion of TP in doses ranging fom 2.5 to 10.0 gm. The effects of TP on the secretion of cortisol, growth hormone, prolactin and thyrotropin will be examined. Initially, the optimal dose of TP to elicit hormonal responses will be established. This dose will then be used to examine hormonal responses in 10 male and 10 female healthy control subjects. In males, studies will be carried out comparing test-retest reliability with TP and comparing hormonal responses to TP and to saline. In females, the effects of menstrual cycle phase on hormonal responses to TP will be examined. Finally, the relationship between plasma TP concentration and hormonal responses will be evaluated. These studies should provide clear evidence concerning the utility of TP as a neuroendocrine provocative agent. If TP should prove to be an effective agent to stimulate hormonal secretion, it would have important applications in studies of patients with major depressive, disorder.